7-74309592-A-T

Position:

• chr7-74309592-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003388.5(CLIP2):​c.-67-7888A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.762 in 151,080 control chromosomes in the GnomAD database, including 43,858 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.76 (43858 hom., cov: 31)
• Consequence: CLIP2 NM_003388.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.904

Genes affected

CLIP2 (HGNC:2586): (CAP-Gly domain containing linker protein 2) The protein encoded by this gene belongs to the family of cytoplasmic linker proteins, which have been proposed to mediate the interaction between specific membranous organelles and microtubules. This protein was found to associate with both microtubules and an organelle called the dendritic lamellar body. This gene is hemizygously deleted in Williams syndrome, a multisystem developmental disorder caused by the deletion of contiguous genes at 7q11.23. Alternative splicing of this gene generates 2 transcript variants. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.805 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLIP2	NM_003388.5	c.-67-7888A>T		intron_variant		ENST00000223398.11	NP_003379.4
CLIP2	NM_032421.3	c.-67-7888A>T		intron_variant			NP_115797.2
CLIP2	XM_047420800.1	c.-67-7888A>T		intron_variant			XP_047276756.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLIP2	ENST00000223398.11	c.-67-7888A>T		intron_variant		5	NM_003388.5	ENSP00000223398.6
CLIP2	ENST00000361545.9	c.-67-7888A>T		intron_variant		1		ENSP00000355151.5

Frequencies

GnomAD3 genomes AF: 0.762 AC: 115077 AN: 150952 Hom.: 43820 Cov.: 31

Gnomad AFR AF: 0.761

Gnomad AMI AF: 0.844

Gnomad AMR AF: 0.799

Gnomad ASJ AF: 0.731

Gnomad EAS AF: 0.826

Gnomad SAS AF: 0.688

Gnomad FIN AF: 0.750

Gnomad MID AF: 0.768

Gnomad NFE AF: 0.758

Gnomad OTH AF: 0.765

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.762 AC: 115175 AN: 151080 Hom.: 43858 Cov.: 31 AF XY: 0.761 AC XY: 56125 AN XY: 73758

Gnomad4 AFR AF: 0.761

Gnomad4 AMR AF: 0.800

Gnomad4 ASJ AF: 0.731

Gnomad4 EAS AF: 0.826

Gnomad4 SAS AF: 0.687

Gnomad4 FIN AF: 0.750

Gnomad4 NFE AF: 0.758

Gnomad4 OTH AF: 0.767

Alfa AF: 0.763 Hom.: 5161

Bravo AF: 0.767

Asia WGS AF: 0.718 AC: 2497 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.025
DANN	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs229881; hg19: chr7-73723922;